我々 は、我々 の研究プロジェクトの中に獣医師、看護士、および彼らの継続的な支援のための生物医学研究のセンターで、動物のキーパーを感謝します。著者は、このプロトコルのすべての校閲者の重要な入力を認めます。オーストリア消化器病学会・肝臓 (ÖGGH) PS に「若手科学賞」と「シュコダ賞」TR 内科のオーストリア社会のいくつか研究資金を供給されました。

<ol>
	<li>Ripoll, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hepatic+venous+pressure+gradient+predicts+clinical+decompensation+in+patients+with+compensated+cirrhosis.">Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis.</a> Gastroenterology. 133 (2), 481-488 (2007).</li><li>Bosch, J., Groszmann, R. J., Shah, V. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evolution+in+the+understanding+of+the+pathophysiological+basis+of+portal+hypertension:+How+changes+in+paradigm+are+leading+to+successful+new+treatments.">Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments.</a> J Hepatol. 62, S121-S130 (2015).</li><li>Blachier, M., Leleu, H., Peck-Radosavljevic, M., Valla, D. C., Roudot-Thoraval, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+burden+of+liver+disease+in+Europe:+a+review+of+available+epidemiological+data.">The burden of liver disease in Europe: a review of available epidemiological data.</a> J Hepatol. 58 (3), 593-608 (2013).</li><li>Colle, I., Geerts, A. M., Van Steenkiste, C., Van Vlierberghe, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+Changes+in+Splanchnic+Blood+Vessels+in+Portal+Hypertension.">Hemodynamic Changes in Splanchnic Blood Vessels in Portal Hypertension.</a> Advances in Integrative Anatomy and Evolutionary Biology. 291 (6), 699-713 (2008).</li><li>Laleman, W., Van Landeghem, L., Wilmer, A., Fevery, J., Nevens, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Portal+hypertension:+from+pathophysiology+to+clinical+practice.">Portal hypertension: from pathophysiology to clinical practice.</a> Liver International. 25 (6), 1079-1090 (2005).</li><li>Franchis, R. d. . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Updating+Consensus+in+Portal+Hypertension:+Report+of+the+Baveno+III+Consensus+Workshop+on+definitions,+methodology+and+therapeutic+strategies+in+portal+hypertension.">Updating Consensus in Portal Hypertension: Report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension.</a> Journal of Hepatology. 33 (5), 846-852 (2000).</li><li>Zardi, E. 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C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+portal+hypertension.">Animal models of portal hypertension.</a> World Journal of Gastroenterology : WJG. 12 (41), 6577-6584 (2006).</li><li>Reiberger, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sorafenib+attenuates+the+portal+hypertensive+syndrome+in+partial+portal+vein+ligated+rats.">Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats.</a> Journal of Hepatology. 51 (5), 865-873 (2009).</li><li>Schwabl, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pioglitazone+decreases+portosystemic+shunting+by+modulating+inflammation+and+angiogenesis+in+cirrhotic+and+non-cirrhotic+portal+hypertensive+rats.">Pioglitazone decreases portosystemic shunting by modulating inflammation and angiogenesis in cirrhotic and non-cirrhotic portal hypertensive rats.</a> Journal of Hepatology. 60 (6), 1135-1142 (2014).</li><li>Reiberger, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nebivolol+treatment+increases+splanchnic+blood+flow+and+portal+pressure+in+cirrhotic+rats+via+modulation+of+nitric+oxide+signalling.">Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling.</a> Liver International. 33 (4), 561-568 (2013).</li><li>Schwabl, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+FXR+agonist+PX20606+ameliorates+portal+hypertension+by+targeting+vascular+remodelling+and+sinusoidal+dysfunction.">The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.</a> Journal of Hepatology. 66 (4), 724-733 (2017).</li><li>Mandorfer, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sustained+virologic+response+to+interferon-free+therapies+ameliorates+HCV-induced+portal+hypertension.">Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension.</a> J Hepatol. 65 (4), 692-699 (2016).</li><li>Schwabl, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interferon-free+regimens+improve+portal+hypertension+and+histological+necroinflammation+in+HIV/HCV+patients+with+advanced+liver+disease.">Interferon-free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease.</a> Aliment Pharmacol Ther. 45 (1), 139-149 (2017).</li><li>Reiberger, T., Mandorfer, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beta+adrenergic+blockade+and+decompensated+cirrhosis.">Beta adrenergic blockade and decompensated cirrhosis.</a> Journal of Hepatology. 66 (4), 849-859 (2017).</li><li>Reiberger, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Carvedilol+for+primary+prophylaxis+of+variceal+bleeding+in+cirrhotic+patients+with+haemodynamic+non-response+to+propranolol.">Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.</a> Gut. 62 (11), 1634-1641 (2013).</li><li>Reiberger, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Austrian+consensus+guidelines+on+the+management+and+treatment+of+portal+hypertension+(Billroth+III).">Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth III).</a> Wiener klinische Wochenschrift. 129 (3), 135-158 (2017).</li><li>de Franchis, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expanding+consensus+in+portal+hypertension.">Expanding consensus in portal hypertension.</a> Journal of Hepatology. 63 (3), 743-752 (2015).</li><li>Pinter, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+sorafenib+on+the+portal+hypertensive+syndrome+in+patients+with+liver+cirrhosis+and+hepatocellular+carcinoma+-+a+pilot+study.">The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma - a pilot study.</a> Alimentary Pharmacology &amp; Therapeutics. 35 (1), 83-91 (2012).</li><li>Schwabl, P., Laleman, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+treatment+options+for+portal+hypertension.">Novel treatment options for portal hypertension.</a> Gastroenterol Rep (Oxf). 5 (2), 90-103 (2017).</li><li>Klein, S., Schierwagen, R., Uschner, F., Trebicka, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Mouse and Rat Models of Induction of Hepatic Fibrosis and Assessment of Portal Hypertension. , (2017).</li><li>Russell, W. M. S., Burch, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Principles of Humane Experimental Technique. , (1959).</li><li>Langhans, W., Myrtha, A., Riediger, T., Lutz, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Routine animal use procedures. , (2016).</li><li>Animal Care and Use Program. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Rat and Mouse anesthesia and analgesia: Formulary and General Drug Information. , (2016).</li><li>Davis, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Current Protocols in Neuroscience. , (2001).</li><li>Albrecht, M., Henke, J., Tacke, S., Markert, M., Guth, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+isoflurane,+ketamine-xylazine+and+a+combination+of+medetomidine,+midazolam+and+fentanyl+on+physiological+variables+continuously+measured+by+telemetry+in+Wistar+rats.">Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats.</a> BMC Veterinary Research. 10 (1), 198 (2014).</li><li>Redfors, B., Shao, Y., Omerovic, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+anesthetic+agent,+depth+of+anesthesia+and+body+temperature+on+cardiovascular+functional+parameters+in+the+rat.">Influence of anesthetic agent, depth of anesthesia and body temperature on cardiovascular functional parameters in the rat.</a> Laboratory Animals. 48 (1), 6-14 (2014).</li><li>Becker, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Statement on anesthesia methodologies: Recommondations on anaesthesia methodologies for animal experimentation in rodents and rabbits. , (2016).</li></ol>

著者が明らかに何もありません。

PP はポータルの高血圧症の評価のための主な成果パラメーターで、基になる肝硬変の重症度を反映しています。マトリックス法 (すなわち、線維症) と正弦波の収縮 (ために血管収縮薬の肝の発現を増加および血管拡張薬に対する反応性の低下) を引き起こす増加 IHVR。複数の臨床11,12,13,14と臨床15,16, PP と慢性肝疾患への影響の重要性が示されています。17,18します。 したがって、肝硬変症患者の PP は難しい結果パラメーターとその軽減、治療のガイドライン19、20 、現在の肝臓の主な研究目的によって推奨されています。包括的な動物モデルを特徴付けるし、PHT22の16,21新しい治療オプションに変換が必要です。このプロトコルは、門脈圧、胃壁循環、内臓の血管拡張、肝内性の評価を含む詳細な血行動態評価に必要な方法論を提示します。代表および齧歯動物モデルから完全血行動態のデータ セットを達成するために経験と実行する演算子の訓練は最も重要なは。
深刻な出血の予防と管理は、特に重要なスキルです。関心の血管のセクションの鈍的かつ正確な準備は、カニュレーション障害と重度の出血を避けるために重要です。重要な血損失、血行動態に大きな影響と PP の正確な測定を排除または実験動物の死でも結果を可能性があります。プロトコルで測定中に発生した、重大度、出血の場所を特徴付けるドキュメント出血。
注記のうち、血流を評価するために血管超音波流れプローブを使用して近似値を生成し、読み取りエラー別の容器のサイズと不適切なプローブの配置のためにさらされる可能性があります。血流と特に血流分布 (門脈体循環シャントの計算を含む) を測定する別の方法は、色の微粒子技術23です。しかし、全臓器は収穫、解散し、分析する必要があります、この省略や発現解析、組織を実行する可能性。したがって、超音波法は動物研究で '3 r' の原則をサポートしています (削減、調整、および交換) ラッセルとトリーバーチ24で。さらに、流量、色の微粒子技術時間をかけて臓器 (腸間膜血行) を統合する必要がリアルタイムでその他の血行動態パラメーターに平行内臓血流を監視する適しています。また、色の微粒子は、通常 15 μ m の直径を持つ、閉じ込められたと不動になることを避けるためにそれぞれの器官の直径の < 15 μ m 微小血管の分布が必要、かもしれない肝硬変肝臓の場合。
このメソッドの主な制限は、動物の PHT 症候群の血行動態の評価中に無意識と麻酔の状態の必要性です。最も一般的で広く使用されている注射麻酔のケタミン ・ キシラジン麻酔25,26の必要な深さを取得する 30-45 分後 redosing がかかるこれは、トラブルシューティングが必要な場合に特に時間圧力を追加します。吸入麻酔を使用して多くの利点が含まれますが、特別な装置が必要と安全規制関連揮発性麻酔薬に従わなければなりません。麻酔深度は、麻酔濃度を調整することによって手術の手順と干渉することがなく迅速に対応できます。気管内チューブは、ケタミン、換気により救済の活性化により、十分な酸素化と換気27麻酔による死の危険を低くための動物の特に後に航空を保護します。ケタミン ・ キシラジンはまだ広く使用されている低用量のイソフルラン麻酔とラット28,29は血行動態または心血管系パラメーターの変化が著しい原因ありません。
現地での経験と規制は、最先端の推奨事項と麻酔科のベスト ・ プラクティスと研究者がこれらの血行動態評価30を実行に使用される麻酔の種類を再考しなければならない継続的を提供します。今後の実験計画は、現在制限に関する一般的な麻酔を克服し、意識した動物の血行動態の評価を許可する注入無線圧力トランスデューサー、テレメトリを使用でしょう。

PHT は静脈瘤出血、腹水1など肝硬変患者の重篤な合併症を引き起こす可能性が、門脈系の病理組織学的に高められた血圧として定義されます。一方、(例えば、門脈血栓症) 前の肝と後肝 (例えばバッド ・ キアリ症候群) PHT はまれ、肝硬変による肝内 PHT PHT2の最も一般的な原因を表します。
肝硬変、PP は主に高架の IHVR3の結果として増加します。高度な段階で PHT は、心拍出量の増加により増加の PVBF によって悪化、全身や内臓の血管抵抗を減少-ポータル高血圧症候群4を定義します。オームの法則 (ΔP = Q * R) IHVR と血流が PP5に比例していることを意味します。患者では、PP の直接測定、危険なない日常的に行われます。代わりに、肝静脈圧力勾配 (化する) は、PP6、7の間接的な指標として使用されます。化するは、肝静脈8は、バルーンカテーテルを使用して測定されるくさび肝静脈圧 (WHVP) から無料肝静脈圧 (FHVP) を減算することによって計算されます。生理化する範囲 1-5 mmHg、間、化する ≥10 mmHg 臨床的に重要な門脈圧亢進症 (CSPH) を定義し、食道静脈瘤出血、腹水、肝性脳症9 など、PHT 関連の合併症のリスクの増加を示す.PP (すなわち化する) は PHT の重大度、PHT の他のコンポーネントに関する情報の最も関連するパラメーターが胃壁循環 (HR、マップ) の重症度を含む内臓/腸間膜血流と IHVR、ために欠かせないPHT の異なる機構の包括的な理解を得る。
したがって、人間の PP の間接測定と対照をなしてラットの導入方法論は PP の直接測定の利点を提供、ポータル高血圧症候群追加血行動態パラメーターの録音が可能します。さらに、PP の直接測定は、肝線維症 (IHVR の主要な決定要因) の量の優れた統合読み出しと肝組織標本誤差に関連線維症の定量化の特定の限界を克服します。
手術胆管結紮 (BDL)、毒素誘起肝障害 (すなわち、四塩化炭素、チオアセトアミド、またはジメチルニトロソアミン管理によって)、食事誘発代謝肝臓などの肝硬変 PHT の最も一般的に使用される齧歯動物モデル疾患モデル。肝 (非硬変) PHT は部分的門脈結紮 (PPVL)10によることができます。
小さい齧歯動物はマウス、ハムスター、ラットまたはウサギを含む、提案手法に適して、比較的低いメンテナンス コストに関連付けられています。それにもかかわらずラットまたは動物のサイズの利点のための大きい齧歯動物で血行動態の評価はマウスより良い精度と再現性で実行することは不可能、すべて見られています。また、特定のマイクロ機器および装置は、マウスと同様の血行動態パラメーターを取得する必要です。最後に、ラットは、下の関連する罹患率と死亡率をより強固としたがって、ドロップ アウト率が低い群に比べてマウスの可能性が高い。
説明されている方法は (すなわち、抗線維化または抗炎症薬) 肝臓の病気の特定の治療法の評価に適してまたはその影響血管緊張や内皮細胞生物学の新規薬理学的アプローチPHT のしたがって、可能性があります効果血行動態パラメーター。

<table><tbody><tr><td>&lt;strong&gt;Instruments&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>LabChart 7 Pro software</td><td>ADInstruments, Colorado Springs, CO, USA</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Software&lt;/em&gt;</td></tr><tr><td>ML870 PowerLab 8/30</td><td>ADInstruments, Colorado Springs, CO, USA</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Electronic multichannel recorder&lt;/em&gt;</td></tr><tr><td>MLT0380/D</td><td>ADInstruments, Colorado Springs, CO, USA</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Pressure transducer (x2: for Portal Pressure and Arterial Pressure)&lt;/em&gt;</td></tr><tr><td>ML112 Quad Bridge Amplifier</td><td>ADInstruments, Colorado Springs, CO, USA</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Bridge amplifier&lt;/em&gt;</td></tr><tr><td>TS420</td><td>Transonic Systems Inc., Ithaca, NY, USA</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Flowmeter module&lt;/em&gt;</td></tr><tr><td>Biological Research Apparatus 7025</td><td>UGO BASILE S.R.L., Comerio, Italy</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Ventilator&lt;/em&gt;</td></tr><tr><td>Vapor 2000</td><td>Dr&amp;auml;ger Medical AG &amp;amp; Co. KG, L&amp;uuml;beck, Germany</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Isofluran Vaporizer&lt;/em&gt;</td></tr><tr><td>Perivascular probes (rat) for Transonic systems (Superior Mesenteric Artery)</td><td>Transonic Systems Inc., Ithaca, NY, USA</td><td>#MA1PRB</td><td>&lt;em&gt;Ultrasonic flow probe (1mm)&lt;/em&gt;</td></tr><tr><td>Perivascular probes (rat) for Transonic systems (Portal Vein)</td><td>Transonic Systems Inc., Ithaca, NY, USA</td><td>#MA2PSB</td><td>&lt;em&gt;Ultrasonic flow probe (2mm)&lt;/em&gt;</td></tr><tr><td>1st for intubation &amp;amp; 2nd for clean skin incisions</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Mayo scissor [x2]&lt;/em&gt;</td></tr><tr><td>&lt;em&gt;Metzenbaum scissor&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Cuticle scissor&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>e.g. Adson Brown tissue forceps</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Tissue Forceps&lt;/em&gt;</td></tr><tr><td>&lt;em&gt;High precision 45&amp;deg; angle broad point forceps [x2]&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Hemostat [x4]&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>e.g. Mikulicz peritoneal clamp</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Curved clamp&lt;/em&gt;</td></tr><tr><td>e.g. Dieffenbach clamp</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Micro clamp&lt;/em&gt;</td></tr><tr><td>e.g. micro spatula with flat ends, width 4 mm,</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Micro metal spatula&lt;/em&gt;</td></tr><tr><td>for transbuccal suture at intubation</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Needle holder&lt;/em&gt;</td></tr><tr><td>&lt;em&gt;Scalpel grip&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>selfmade</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Intubation desk&lt;/em&gt;</td></tr><tr><td>blut, flexible and with a suitable diameter for arterial cannula and venflow</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Blunt steel wire&lt;/em&gt;</td></tr><tr><td>modified arterial line 20G with Flowstich</td><td>Becton Dickinson, Farady Road, Swindon, UK</td><td>#682245</td><td>&lt;em&gt;Arterial line&lt;/em&gt;</td></tr><tr><td>&lt;em&gt;Heating pad&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Rectal temerature probe&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Saline heater&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Laryngoscope (specific for animal size, e.g. rat)&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Inductionbox for inhalation anesthesia&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Scale (able to measure mg)&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;em&gt;Hair clipper&lt;/em&gt;</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td><td>&amp;nbsp;-</td></tr><tr><td>&lt;strong&gt;Name &lt;/strong&gt;</td><td>&lt;strong&gt;Company &lt;/strong&gt;</td><td>&lt;strong&gt;Catalog Number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>&lt;strong&gt;Consumables &lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>e.g. modified BD Venflon Pro Safety 14GA</td><td>Becton Dickinson Infusion Therapy, AB, SE251 06 Helsingborg, Sweden</td><td>#393230</td><td>&lt;em&gt;Peripheral venous catheter (14G)&lt;/em&gt;</td></tr><tr><td>Fine-Bore Polyethylene Tubing, ID 0.58mm, OD 0.96mm, Portex,</td><td>Smiths Medical International Ltd., Kent, UK</td><td>#800/100/200</td><td>&lt;em&gt;Catheter tube (PE-50)&lt;/em&gt;</td></tr><tr><td>e.g. Omnifix-F Solo</td><td>B. Braun Melsungen AG, Melsungen, Germany</td><td>#9161406V</td><td>&lt;em&gt;Syringe 1mL&lt;/em&gt;</td></tr><tr><td>e.g. Injekt Solo</td><td>B. Braun Melsungen AG, Melsungen, Germany</td><td>#4606051V</td><td>&lt;em&gt;Syringe 5mL&lt;/em&gt;</td></tr><tr><td>e.g. Injekt Solo</td><td>B. Braun Melsungen AG, Melsungen, Germany</td><td>#4606205V</td><td>&lt;em&gt;Syringe 20mL&lt;/em&gt;</td></tr><tr><td>e.g. BD Microlance 3, 18G - 1 1/2&quot;</td><td>Becton Dickinson S.A., Fraga, Spain</td><td>#304622</td><td>&lt;em&gt;Cannula (18G)&lt;/em&gt;</td></tr><tr><td>e.g. BD Microlance 3, 23G - 1&quot;</td><td>Becton Dickinson S.A., Fraga, Spain</td><td>#300800</td><td>&lt;em&gt;Cannula (23G)&lt;/em&gt;</td></tr><tr><td>e.g. BD Microlance 3, 30G - 1/2&quot;</td><td>Becton Dickinson S.A., Fraga, Spain</td><td>#304000</td><td>&lt;em&gt;Cannula (30G) &lt;/em&gt;</td></tr><tr><td>e.g. Leukoplast S</td><td>BSN medical GmbH, Hamburg,&amp;nbsp; Germany</td><td>#47619-00</td><td>&lt;em&gt;Adhesive tape&lt;/em&gt;</td></tr><tr><td>e.g. Gazin RK Mullkompressen (18x8cm)</td><td>Lohmann &amp;amp; Rauscher, Vienna, Austria</td><td>#10972</td><td>&lt;em&gt;Gauze compress (small)&lt;/em&gt;</td></tr><tr><td>e.g. Gazin RK Mullkompressen (5x5cm)</td><td>Lohmann &amp;amp; Rauscher, Vienna, Austria</td><td>#10961</td><td>&lt;em&gt;Gauze compress (big)&lt;/em&gt;</td></tr><tr><td>Silk Braided black, USP 4/0, EP 1.5</td><td>SMI AG, St. Vith, Belgium</td><td>#2021-04</td><td>&lt;em&gt;Suture (Silk 4/0, EP 1.5)&lt;/em&gt;</td></tr><tr><td>e.g. Mersilk, 2-0 (3 Ph. Eur.), PS-1 Prime</td><td>Johnson &amp;amp; Johnson Medical GmbH - Ethicon Deutschland, Germany</td><td>#EH7552</td><td>&lt;em&gt;Transbuccal suture&lt;/em&gt;</td></tr><tr><td>e.g. Cottonbuds (2.2mm, 15cm)</td><td>Paul Hartmann AG, Heidenheim, Germany</td><td>#967936</td><td>&lt;em&gt;Cotton buds&lt;/em&gt;</td></tr><tr><td>e.g. Vue Ultrasoundgel</td><td>Optimum Medical Limited, UK</td><td>#1157</td><td>&lt;em&gt;Ultrasound gel&lt;/em&gt;</td></tr><tr><td>e.g. Glubran 2</td><td>Gem srl, Viareggio, Italy</td><td>#G-NB2-50</td><td>&lt;em&gt;Tissue glue&lt;/em&gt;</td></tr><tr><td>e.g. Surgical scalpell knife Nr. 10 - carbon steel</td><td>Swann-Morton, England, B.S.</td><td>#202</td><td>&lt;em&gt;Scalpel Knife&lt;/em&gt;</td></tr><tr><td>Heparin, 5000 i.E./mL (Natriumheparin)</td><td>Medicamentum Pharma GmbH, Allerheiligen im M&amp;uuml;rztal, Austria</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Heparin&lt;/em&gt;</td></tr><tr><td>Florane</td><td>Aesica Queenborough Ltd., Queenborough, UK</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Isoflurane&lt;/em&gt;</td></tr><tr><td>OeloVital (5g)</td><td>Fresenius Kabi Austira Gmbh, Graz, Austria</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Eye gel&lt;/em&gt;</td></tr><tr><td>Ketasol</td><td>aniMedica GmbH, Senden-B&amp;ouml;sensell, Germany</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Ketamine&lt;/em&gt;</td></tr><tr><td>Rompun</td><td>Bayer Austria Ges.m.b.H., Vienna, Austria</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Xylazine&lt;/em&gt;</td></tr><tr><td>Xylocain 10% Pumpspray</td><td>AstraZeneca &amp;Ouml;sterreich GmbH, Vienna, Austria</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Lidocaine pump spray&lt;/em&gt;</td></tr><tr><td>Dipidolor</td><td>Jansen-Cilag Pharma GmbH, Vienna, Austria</td><td>&amp;nbsp;-</td><td>&lt;em&gt;Piritramide&lt;/em&gt;</td></tr><tr><td>NaCl 0.9% Fresenius, 1L</td><td>Fresenius Kabi Austira GmbH, Graz, Austria</td><td>#13LIP132</td><td>&lt;em&gt;Physiological saline solution&lt;/em&gt;</td></tr></tbody></table>

invasive hemodynamic characterization of the portal-hypertensive syndrome in cirrhotic rats

これは、ポータルの高血圧症候群の特性評価のための肝硬変ラットにおける侵襲血行動態測定を記述する詳細なプロトコルです。肝硬変による門脈圧亢進症 (PHT) は肝疾患の最も重篤な合併症を担当です。ポータル高血圧症候群の全体像は、肝内血管抵抗 (IHVR) の増加、胃壁の循環、内臓の血流増加による増加ポータル圧力 (PP) が特徴です。進歩的な内臓動脈の血管拡張や高い心拍数 (HR) が低の動脈圧と心拍出量の増加ポータル高血圧症候群の特徴です。
新規治療法は現在、いずれかのターゲット IHVR で PP を減らすことを目指すを開発されているまたは内臓の血流を増加-全身の血行動態に対する副作用が発生します。静脈、内臓、ポータルと全身血行動態的パラメーターの詳細な特性解析は、PP、門脈血流量 (PVBF)、上腸間膜動脈の血流、平均動脈圧 (地図)、および HR の測定を含めたに必要なため、前臨床PHT 新たな治療法の有効性の評価。私たちのビデオの記事は、肝硬変ラットにおける侵襲血行動態計測を実行するための構造化されたプロトコルを持つリーダーを提供します。特に、大腿動脈と回盲部静脈を介して門脈カテーテルおよび静脈のポータルの測定について述べるし、内臓の血流の血管ドップラー超音波流れプローブを介して。PHT の異なるラット モデルの代表の結果が表示されます。

動物モデルと肝疾患の重症度、に応じて PHT の度ポータル高血圧症候群の重症度は、異なる (図 7)。
BDL モデルは、胆汁うっ滞による胆汁性肝硬変を引き起こします。したがって、PP 増加時間と、胃壁の循環を開発し、HR の増加と減少の地図で見られるように。肝硬変動物、SMABF、PVBF、IHVR も的外れに増資肝と血行動態の変化 (図 7 a-F)
対照的に、PPVL により、非硬変肝の PHT PP の即時増加し全身の血行動態の変化によって特徴付けられる (図 7-私)。ただし、経門脈中に担保を開発これは PP を下げる可能性があります。
Sham 動物の血行動態の値は、生理学的なレベルでは、時間をかけて大幅に変更しないでください。健康など動物の門脈圧は最大の 6 に 5 mmHg (図 7J L) です。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57261/57261fig1.jpg"> 図 1: 自作気管挿管デバイス:(A) 気管内チューブ。(B) ガイドはワイヤー デバイス (C) 挿管デスクです。(D) 管はガイド ワイヤ デバイスに接続されています。<a href="/files/ftp_upload/57261/57261fig1large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57261/57261fig2.jpg"> 図 2: 術前準備:(A) 動物の挿管。(B) 筋肉と皮下注射麻酔。動物の暖房のマットの固定を (C)。(D) 置くと直腸温度プローブを固定します。<a href="/files/ftp_upload/57261/57261fig2large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/57261/57261fig3.jpg"> 図 3: 心拍数 (HR)、平均動脈圧 (地図):(A) 皮膚切開をします。(B) 準備、大腿の血管と神経の構造。(C-F)大腿動脈解離。(G) 遠位縫合、固定 - 近位前近位縫合糸を結び目。(H) 大腿動脈カテーテルの準備。(私) 血管マイクロ鉗子の配置。(J) 穿孔曲げ針で大腿動脈。大腿動脈のカテーテル治療 (K)。(L) マイクロ クランプ パルスの評価のための開口部。(M) 近位カテーテル固定。(N) カテーテルの遠位固定。(O) 測定の地図と時間 (P) を浸した小さなガーゼ外科分野をカバーを圧縮します。<a href="/files/ftp_upload/57261/57261fig3large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/57261/57261fig4.jpg"> 図 4: 優れた腸間膜動脈血流 (SMABF):(A-C)術を施行しました。(D) 移動性盲腸の発掘。(E-F)腸の発掘。浸したガーゼ湿布で腸のラップを (G)。(H-K)鈍カニューレ フックと内臓の腸間膜動脈の準備。(L, M)フロー プローブの添付ファイル。超音波の (N) アプリケーションにジェルが流れプローブ センサー。(O) の正しい '非収縮性' 配置、フロー プローブの。(P) SMABF の測定。<a href="/files/ftp_upload/57261/57261fig4large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/57261/57261fig5.jpg"> 図 5: 門脈血流量 (PVBF):(A) 最適化された背観門脈 (B) 腸間膜の脂肪質のティッシュから門脈の解剖。門脈血流プローブの組織トンネルを作成する (C)。(D, E)門脈に流プローブの添付ファイル。超音波の (F) アプリケーションにジェルが流れプローブ センサー。(G) 流プローブの正しい '非収縮性' 配置。PVBF を測定する (H)。<a href="/files/ftp_upload/57261/57261fig5large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/57261/57261fig6.jpg"> 図 6: 門脈圧 (PP):(A) カテーテルの準備。(B) 腸の準備。(C) 最適化をメインの上腸間膜静脈の血管に表示します。(D) 穿孔臓側腹膜とカテーテルに適した近い血管分岐の進歩。(E) 主枝と側枝の接合角度で回盲部の静脈のカテーテル法。肝門部に近い門脈にカテーテル先端部の (F) 進出。(G, H)PP. の測定<a href="/files/ftp_upload/57261/57261fig6large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。
<img alt="Figure 7" class="xfigimg" src="/files/ftp_upload/57261/57261fig7v2.jpg"> 図 7: 代表結果:(A) PP、(B) マップ、および BDL ラット (C) HR の時間コース。したがって、(D) SMABF (E) PVBF ・ IHVR (F) の変化が観察されます。PPVL で PP (G)、(H) マップ、および (私) HR の血行動態が手術後初期に最も顕著します。健康的な偽手術 (従って) 動物 (J) PP (K) 地図と (L) HR 生理値内に残っている、時間の経過とともに変更しないでください。<a href="/files/ftp_upload/57261/57261fig7v2large.jpg" target="_blank">この図の拡大版を表示するのにはここをクリックしてください</a>。

Watch this Scientific Journal Video about Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats at JoVE.com

Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

ここでラットのポータル高血圧症候群を特徴付けるために門脈圧、内臓の血流、血行などの循環パラメーターの侵襲的な測定のための詳しいプロトコルについて述べる。

肝硬変ラットにおけるポータル高血圧症侵襲血行動態評価

This is a detailed protocol describing invasive hemodynamic measurements in cirrhotic rats for the characterization of portal hypertensive syndrome. ...

invasive-hemodynamic-characterization-portal-hypertensive-syndrome

Universidad San Sebastian

Research

JoVE Journal

Medicine

15.0K ビュー.  Medical University of Vienna, Vienna, Austria. ここでラットのポータル高血圧症候群を特徴付けるために門脈圧、内臓の血流、血行などの循環パラメーターの侵襲的な測定のための詳しいプロトコルについて述べる。

ビデオ: Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2).
A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.&#160; The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor&#8217;s portal vein was carried out via the recipient&#8217;s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient&#8217;s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7
In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3&#177;0.8 g to 9.8&#177;1 g. At this time, the graft&#8217;s weight decreased from 3.3&#177;0.8 g to 2.3&#177;0.8 g.
We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates.

Auxiliary liver transplantation provides a temporary support in acute hepatic failure, until regeneration of the failing liver. The heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) renders sufficient liver function. We developed an analogous technique in the rat, to examine the influence of the portal vein arterialization on the morphology and function of the graft.

急性肝障害における流れ調節性門脈動脈血と異補助ラット肝移植

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the ...

医学

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. However, due to the small size of the mouse, technical details of the intraoperative monitoring procedure suitable for the mouse were rarely described. Previously we have reported a monitoring procedure to obtain hemodynamic parameters for rats. Now, we adapted the procedure to acquire systemic and hepatic hemodynamic parameters in mice, a species ten-fold smaller than rats. This film demonstrates the instrumentation of the animals as well as the data acquisition process needed to assess systemic and hepatic hemodynamics in mice. Vital parameters, including body temperature, respiratory&#160;rate&#160;and heart&#160;rate were recorded throughout the whole procedure. Systemic hemodynamic parameters consist of carotid artery pressure (CAP) and central venous pressure (CVP). Hepatic perfusion parameters include portal vein pressure (PVP), portal flow rate as well as the flow rate of the common hepatic artery (table 1). Instrumentation and data acquisition to record the normal values was completed within 1.5 h. Systemic and hepatic hemodynamic parameters remained within normal ranges during this procedure.
This procedure is challenging but feasible. We have already applied this procedure to assess hepatic hemodynamics in normal mice as well as during 70% partial hepatectomy and in liver lobe clamping experiments. Mean PVP after resection (n= 20), was 11.41&#177;2.94 cmH2O which was significantly higher (P&#60;0.05) than before resection (6.87&#177;2.39 cmH2O). The results of liver lobe clamping experiment indicated that this monitoring procedure is sensitive and suitable for detecting small changes in portal pressure and portal flow rate. In conclusion, this procedure is reliable in the hands of an experienced micro-surgeon but should be limited to experiments where mice are absolutely needed.

This film demonstrates how to acquire systemic and hepatic hemodynamics in mice. The whole monitoring includes acquisition of vital parameters, systemic blood pressure, central venous pressure, common hepatic artery flow rate, and portal vein pressure as well as the portal flow rate in mice.

マウスにおける全身および肝血行動態パラメータの監視

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. ...

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. 
Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.

Pulmonary arterial hypertension (PAH) is a disease of pulmonary arterioles that leads to their obliteration and the development of right ventricular failure. Rodent models of PAH are critical in understanding the pathophysiology of PAH. Here we demonstrate hemodynamic characterization, with right heart catheterization and echocardiography, in the mouse and rat.

肺動脈性肺高血圧症の齧歯類モデルの血行動態特性評価

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels. To measure the right heart and pulmonary hemodynamics in this model, right heart catheterization is performed by inserting a rigid cannula containing a flexible ball-tip catheter via the right jugular vein into the right ventricle. The catheter is then advanced into the main and the more distal pulmonary arteries. The histopathology of the pulmonary vasculature is assessed qualitatively, by scoring the pre- and intra-acinar vessels on the degree of muscularization and the presence of a neointima, and quantitatively, by measuring the wall thickness, the wall-lumen ratios, and the occlusion score.

This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

流れ誘導性の肺動脈性肺高血圧症のためのラットモデルにおけるシャント手術、右心カテーテル、および血管形態計測

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt ...

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.

Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy ALPPS Procedure

Inducing rapid liver hypertrophy using Associating Liver Partition and Portal vein ligation for a Staged hepatectomy (ALPPS) has been proposed for resection of borderline resectable liver tumors. This model may elucidate mechanisms involved in rapid hypertrophy and allows testing of drugs that promote or block the acceleration of regeneration.

肝のパーティションを関連付けると段階的な肝切除 (ALPPS) プロシージャの門脈結紮ラットモデル

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver ...

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced chronic liver disease followed by an instruction for transjugular biopsy. Under local anesthesia and ultrasound guidance, a catheter introducer sheath is placed in the right internal jugular vein. Using&#160;fluoroscopic guidance, a balloon catheter is advanced into the inferior vena cava (IVC) and inserted into a large hepatic vein. Correct and sufficient wedge position of the catheter is ensured by injecting contrast media while the balloon is blocking the outflow of the cannulated hepatic vein. After calibrating the external pressure transducer, continuous pressure recordings are obtained with triplicate recordings of the wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP). The difference between FHVP and WHVP is referred to as HVPG, with values &#8805;10 mm Hg indicating clinically significant portal hypertension (CSPH). Before removing the catheter, pressure readings obtained in the IVC at the same level, as well as the right atrial pressure are recorded.
Finally, a transjugular liver biopsy can be obtained via the same vascular route. Different systems are available; however, core biopsy needles are preferred over aspiration needles, especially for cirrhotic livers. Again, under fluoroscopic guidance a biopsy needle introducer sheath is advanced into an hepatic vein. Next, the transjugular biopsy needle is gently advanced through the introducer sheath: (i) in case of aspiration biopsy, the needle is advanced into the liver parenchyma under aspiration and then removed quickly, or (ii) in case of a core biopsy, the cutting-mechanism is triggered inside the parenchyma. Several separate passages can be safely performed to obtain sufficient liver specimens via transjugular biopsy. In experienced hands, the combination of these procedures takes about 30-45 min.

Here, we present a protocol for measurement of hepatic venous pressure gradient (HVPG),the gold standard to diagnose clinically significant portal hypertension. Moreover, we describe how to perform a transjugular liver biopsy within the same session.

肝静脈圧勾配と経頸部肝生検の測定

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced ...

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

Here, we describe a setup for simultaneous recording of electrocardiography and intra-arterial blood pressure (BP) in experimental rats, which can be done with standard equipment in animal facilities and can be applied to physiological or pharmacological studies to investigate pathogenic or therapeutic mechanisms in cardiovascular medicine.

心電図の同時記録と侵襲的血圧ラットにおける測定

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. ...

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

マウスにおける右心室系と低酸素誘発性肺動脈高血圧に対する侵襲的血行力学的評価

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. ...

Evaluation of Cerebral Blood Flow Autoregulation in the Rat Using Laser Doppler Flowmetry

When investigating the body&#39;s mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained using laser Doppler flowmetry (LDF). This paper demonstrates a closed skull preparation that allows cerebral blood flow to be assessed without penetrating the skull or installing a chamber or cerebral window. To evaluate autoregulatory mechanisms, a model of controlled blood pressure reduction via graded hemorrhage can be utilized while simultaneously employing LDF. This enables the real time tracking of the relative changes in the blood flow in response to reductions in arterial blood pressure produced by the withdrawal of circulating blood volume. This paradigm is a valuable approach to study cerebral blood flow autoregulation during reductions in arterial blood pressure and, with minor modifications in the protocol, is also valuable as an experimental model of hemorrhagic shock. In addition to evaluating autoregulatory responses, LDF can be used to monitor the cortical blood flow when investigating metabolic, myogenic, endothelial, humoral, or neural mechanisms that regulate cerebral blood flow and the impact of various experimental interventions and pathological conditions on cerebral blood flow.

This article demonstrates the use of laser Doppler flowmetry to evaluate the ability of the cerebral circulation to autoregulate its blood flow during reductions in arterial blood pressure.

レーザードップラー流量測定を用いたラットにおける脳血流自動調節の評価

When investigating the body&#39;s mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained ...

Organ Ischemia-Reperfusion Injury by Simulating Hemodynamic Changes in Rat Liver Transplant Model

Orthotopic liver transplantation (OLT) in rats is a tried and proven animal model used for preoperative, intraoperative, and postoperative studies, including ischemia-reperfusion injury (IRI) of extrahepatic organs. This model requires numerous experiments and devices. The duration of anhepatic phase is closely related to the time to develop IRI after transplantation. In this experiment, we used hemodynamic changes to induce extrahepatic organ damage in rats and determined the maximum tolerance time. The time until the most severe organ injury varied for different organs. This method can easily be replicated and can also be used to study IRI of the extrahepatic organs after liver transplantation.

This paper provides a detailed description of how to build an animal model of the anhepatic phase (liver ischemia) in rats to facilitate basic research into ischemia-reperfusion injury after liver transplantation.

ラット肝移植モデルにおける血球力学的変化をシミュレートすることによる臓器虚血再灌流損傷

Orthotopic liver transplantation (OLT) in rats is a tried and proven animal model used for preoperative, intraoperative, and postoperative studies, ...